Hoon S~Nislow C, 2011

Pubmed ID 22384333
Title A global perspective of the genetic basis for carbonyl stress resistance.
Authors Shawn Hoon, Marinella Gebbia, Michael Costanzo, Ronald W Davis, Guri Giaever, Corey Nislow
Abstract The accumulation of protein adducts caused by carbonyl stress (CS) is a hallmark of cellular aging and other diseases, yet the detailed cellular effects of this universal phenomena are poorly understood. An understanding of the global effects of CS will provide insight into disease mechanisms and can guide the development of therapeutics and lifestyle changes to ameliorate their effects. To identify cellular functions important for the response to carbonyl stress, multiple genome-wide genetic screens were performed using two known inducers of CS. We found that different cellular functions were required for resistance to stress induced by methylglyoxal (MG) and glyoxal (GLY). Specifically, we demonstrate the importance of macromolecule catabolism processes for resistance to MG, confirming and extending known mechanisms of MG toxicity, including modification of DNA, RNA, and proteins. Combining our results with related studies that examined the effects of ROS allowed a comprehensive view of the diverse range of cellular functions affected by both oxidative and carbonyl stress. To understand how these diverse cellular functions interact, we performed a quantitative epistasis analysis by creating multimutant strains from those individual genes required for glyoxal resistance. This analysis allowed us to define novel glyoxal-dependent genetic interactions. In summary, using multiple genome-wide approaches provides an effective approach to dissect the poorly understood effects of glyoxal in vivo. These data, observations, and comprehensive dataset provide 1) a comprehensive view of carbonyl stress, 2) a resource for future studies in other cell types, and 3) a demonstration of how inexpensive cell-based assays can identify complex gene-environment toxicities.
Citation G3 (Bethesda) 2011; 1:219-31

Datasets

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Papers Phenotype Conditions Collection Tested mutants Data Details
Hoon S~Nislow C, 2011 growth (relative abundance in pooled culture) glyoxal [20 mM] hom 4,247 Quantitative
Hoon S~Nislow C, 2011 growth (relative abundance in pooled culture) methylglyoxal [8 mM] hom ~4,700 Quantitative

Curation history

Tested strains

June 27, 2016 Request sent.
Aug. 17, 2016 Request sent.
Aug. 18, 2016 Loaded.

Data

April 2, 2016 To request.
June 27, 2016 Request sent.
Aug. 17, 2016 Request sent.
Aug. 18, 2016 Loaded.